Leptomeningeal Metastases in Non-small Cell Lung Cancer: Optimal Systemic Management in NSCLC With and Without Driver Mu
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Lung Cancer (HA Wakelee and TA Leal, Section Editors
Leptomeningeal Metastases in Non-small Cell Lung Cancer: Optimal Systemic Management in NSCLC With and Without Driver Mutations Mariam Alexander, MD, PhD Emily Lin, MD Haiying Cheng, MD, PhD* Address * Department of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, 10461, USA Email: [email protected]
* Springer Science+Business Media, LLC, part of Springer Nature 2020
This article is part of the Topical Collection on Lung Cancer Keywords Leptomeningeal I Lung cancer I Targeted therapies I EGFR mutations
Opinion statement As a devastating complication of non-small cell lung cancer (NSCLC), the incidence of leptomeningeal metastasis (LM) is rising, largely due to overall longer survival of NSCLC, especially in patients with targetable molecular driver mutations. There is no clear consensus on the optimal management of LM. This review will cover recent advances in diagnosis, monitoring, and treatment of LM in NSCLC. In LM without oncogene drivers, systemic chemotherapy, intrathecal therapy, and radiation have modestly improved the clinical outcomes. Emerging data have also suggested encouraging activity of immunotherapy. At the same time, in LM with sensitizing EGFR mutations, osimertinib should be considered regardless of T790M status. Pulse erlotinib, afatinib, and newer agents with improved CNS penetration have also shown benefits. Moreover, accumulating evidences support potential benefits of molecularly targeted therapy in ALK-rearranged and other oncogene-driven NSCLC with LM. Future studies are warranted to better define the underlying mechanism, to optimize the clinical management, and to improve patient outcomes.
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Curr. Treat. Options in Oncol.
(2020) 21:72
Introduction Leptomeningeal metastases (LM) or leptomeningeal carcinomatosis is the seeding of tumor cells within the subarachnoid space and leptomeninges [1]. It affects up to 10% of adult patients with solid tumors, especially breast, melanoma, and non-small cell lung cancer (NSCLC) [2]. Dissemination occurs through hematogenous spread, direct seeding through the brain or cranial metastases, and endoneural or perineural routes. The most common sites of LM are base of the brain, sylvian fissure, and cauda equina due to slow flow and gravity. There are currently two types of leptomeningeal
metastasis described by the European Association of Neuro-Oncology (EANO) based on clinical presentation (typical/atypical), cytological presence of tumor cells and MRI findings with type I defined by the presence of tumor cells in the CSF and type II defined by typical clinical and MRI signs [3]. The MRI findings are categorized into 4 types: type A has linear contrast enhancement of the leptomeninges, type B has leptomeningeal nodules, type C is a combination of types A and B while type D has normal MRI findings except for potential hydrocephalus.
Epidemiology and prognosis The prognosis of patients with NSCLC who have LM is poor, with median overall su
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